Copper‐Metallized Porous N‐Heterocyclic Carbene Ligand Polymer‐Catalyzed Regio‐ and Stereoselective 1,2‐Carboboration of Alkynes

Abstract Alkenylboronates are highly versatile building blocks and valuable reagents in the synthesis of complex molecules. Compared with that of monosubstituted alkenylboronates, the synthesis of multisubstituted alkenylboronates is challenging. The copper‐catalyzed carboboration of alkynes is an operationally simple and straightforward method for synthesizing bis/trisubstituted alkenylboronates. In this work, a series of copper‐metallized N‐Heterocyclic Carbene (NHC) ligand porous polymer catalysts are designed and synthesized in accordance with the mechanism of carboboration. By using CuCl@POL‐NHC‐Ph as the optimal nanocatalyst, this study realizes the β‐regio‐ and stereoselective (syn‐addition) 1,2‐carboboration of alkynes (regioselectivity up to >99:1) with satisfactory yields and a wide range of substrates. This work not only overcomes the selectivity of carboboration but also provides a new strategy for the design of nanocatalysts and their application in organic synthesis.

selectivity, and reduced the HOMO-LUMO gap, which have attracted the attention of many chemists.More importantly, they are not only used as solid carriers, but also as ligands for various metal catalysts. [12]As a recyclable catalyst, M/POLs have achieved many organic reactions, such as asymmetric conjugate addition and selective conversion of olefins/alkynes/allenes. [13] We believe that the combination of nanocatalysis and POLs can be used to solve the selectivity problem that cannot be solved under homogeneous conditions.Therefore, we attempted to synthesize a series of copper-metallized six-membered NHC ligand polymer catalysts and the carboboration of alkynes.Our results showed that the NHC catalysts achieved the 1,2-carboboration of alkynes with high regioselectivity (-:-up to >99:1) and stereoselectivity (syn-addition) in the synthesis of alkenylboronates and that the   S4 (Supporting Information).
catalytic system has high efficiency (up to 92% isolated yield) and wide substrate scope (65 examples) for this reaction (Scheme 1C).
We demonstrated the synthetic utility of the disubstituted alkenylboronates synthesized through the above method (Scheme 4A).First, we performed a gram-scale synthesis of 4a under standard conditions.After we scaled up the amount of alkynes by a factor of 20, 4a was still obtained with 85% (2.43 g) isolated yield and >97:3 regioselectivity.The Suzuki-Miyaura coupling of 4a with 4-iodoanisole afforded 5 in 94% yield.Vinyl azide 6 was prepared through a copper-mediated reaction with sodium azide with 62% yield.Furthermore, compound 7, a valuable enol ether for various organic transformations, was obtained readily with 80% yield.Conjugated dienyl ester 8 could be prepared through the oxidative Heck coupling of 4a and tert-butyl acrylate (EE:EZ = 95:5).Vinyl halides (9 10), which are important coupling partners in various transition-metalcatalyzed syntheses, were with good yields of 81% and 85%.Additionally, we synthesized 2-ethynyl-5-propylthiophene 11, which reacted with methyl iodide and B 2 pin 2 at room temperature to generate alkenylboronate 12.The hydrolysis of the ester group was completed after the Suzuki-Miyaura coupling of 12 and methyl 4-iodobenzoate to obtain product 13.Product 13 and the drug molecule namirotene (CBS-211A) are isomers (Scheme 4B).Alkyne 14 reacted with ethyl iodide and B 2 pin 2 to generate trisubstituted alkenylboronate 15 (74% yield, >99:1).The nonsteroidal estrogen drug diethylstilbestrol was acquired via the Suzuki coupling of 15 with 4-iodoanisole followed by deprotection (Scheme 4B).
As shown in Figure 1 (left), we performed a leaching experiment to investigate whether the reaction was homogeneous or heterogeneous. [15]When the carboboration of phenylacetylene with 1-iodobutane and B 2 pin 2 was performed for 2 h, the GC-MS yield was 39%.When the reaction was continued for 7 h, the final GC-MS yield was 91% (black line).The reaction was conducted for 2 h, the catalyst was removed through filtration, and the solution was further reacted under the same conditions for 7 h.The final GC-MS yield was 49% (red line).In addition, by washing and post-treating the used catalyst, we recycled the nanocatalyst for five cycles (Figure 1 (right)).Leaching and cycle tests demonstrated that the reaction is likely a heterogeneously catalyzed process.
The prepared POL-NHC-Ph and CuCl@POL-NHC-Ph were characterized to study their structure-reactivity relationship (Figure 2).Scanning electron microscopy (SEM) revealed ) TEM image of CuCl@POL-NHC-Ph.c) HAADF image of CuCl@POL-NHC-Ph.d) Energy-dispersive X-ray spectroscopy elemental mapping analysis of CuCl@POL-NHC-Ph.e) N 2 adsorption-desorption isotherms, f) pore size distribution curves, g) Cu 2p XPS spectra of fresh CuCl@POL-NHC-Ph, and h) thermogravimetric analysis of CuCl@POL-NHC-Ph.that POL-NHC-Ph and CuCl@POL-NHC-Ph were porous (Figure 2a).The results of transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), and elemental mapping showed that CuCl was loaded on POL-NHC-Ph in the form of nanoparticles (Figure 2b-d).N 2 adsorptiondesorption analysis revealed that CuCl@POL-NHC-Ph had a Brunauer-Emmett-Teller (BET) surface area of 151.90 m 2 /g and a corresponding total pore volume of 0.31 cm 3 g −1 (Figure 2e,f).Adsorption experiments showed that the catalyst had adsorption effect on phenylacetylene, iodobutane and B 2 pin 2 (Figure S9, Supporting Information).We performed X-ray photoelectron spectroscopy (XPS) on our catalyst to check the valence of the copper species.In contrast to the CuCl 2p photoemission peak (Cu 2p 3/2 and Cu 2p 1/2 binding energies of 932.28 and 952.28 eV, respectively), the XPS peak of CuCl@POL-NHC-Ph had a positive shift of 1.4 eV (Cu 2p 3/2 and Cu 2p 1/2 binding energies of 933.68 and 953.68 eV, respectively), [16] indicating coordination between CuCl and POL-NHC-Ph (Figure 2g).Carbene is a severely electron-deficient structure.When the carbene carbon coordinates with CuCl, the lone pair electrons of the 3d orbital of copper may partially feed back into the empty p orbital of the carbene carbon.Therefore, the electron loss of copper occurs, and the XPS spectrum shows a positive shift.The TG curves of POL-NHC-Ph and CuCl@POL-NHC-Ph demonstrated that the polymer remained intact at temperatures of up to 200 °C (Figure 2h).We also performed the same characterization on metal-free POL-NHC-Ph and used CuCl@POL-NHC-Ph (see Figures S1-S7, Supporting Information).In addition, to obtain information regarding the oxidation state of used copper nanoparticles, the catalyst was analyzed by using XPS, which provided evidence for the presence of Cu(I) and Cu(II) with an estimated ratio of 1.14:1.
Inductively coupled plasma-mass spectrometry revealed that the copper loading of CuCl@POL-NHC-Ph was 4.67 wt.% (Figure S8, Supporting Information).The results of solid-state NMR and infrared spectroscopy of CuCl@POL-NHC-Ph showed that the structure of carbene in the polymer remained intact (Figures S10 and S11, Supporting Information).The characterization results revealed no significant change in the catalyst after use, revealing the superior stability of the catalyst.
We conducted DFT calculations to explain the differences among the four NHC catalysts.We analyzed the natural orbitals of the polymer subunits C1, C2, C3, and C4 (Figure 3).We found that the gap between the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) of C3 was considerably smaller than that of C1, C2, and C4 (Figure 3A).A small gap means that the catalyst facilitates electron transition and that the catalyst has high activity.10e] Surprisingly, the HOMO-LUMO gap of the tetramer of C3 decreased to 386.1 KJ mol −1 , suggesting that polymerization may improve the activity of the catalyst (Figure 3B).
On the basis of the selectivity results of our experiments and related reports on copper-catalyzed alkyne carboboration reactions, [17,4d,h] we proposed a possible reaction process (Scheme 5).The experimental results of unactivated iodoalkane 2f showed that the reaction mechanism was not a free radical process.The catalytically active species B was generated by catalyst A under the action of NaO In summary, we developed a highly regio-and stereoselective method for the 1,2-carboboration of alkynes with a novel recyclable and highly stable heterogeneous nanocatalyst, CuCl@POL-NHC-Ph.We characterized the prepared POL-NHC-Ph and CuCl@POL-NHC-Ph to study their structure-reactivity relationships.TEM images showed that copper NPs were highly discretely distributed in this porous polymer.This distribution pattern resulted in the high activity of this nanocatalyst.The reaction had broad substrate adaptability and good yields.Additionally, the results of DFT calculations showed that among the catalysts, the Cu-NHC complex C3 had the smallest HOMO-LUMO gap, indicating that C3 may have high catalytic activity.We also proposed a possible mechanism for the CuCl@POL-NHC-Phcatalyzed -selective 1,2-carboboration of alkynes.

Table 1 .
Optimization of reaction conditions.